Fine needle aspiration cytodiagnosis of Hodgkin's disease and its subtypes. I. Scope and limitations

The fine needle aspiration (FNA) smears and paraffin-embedded sections from 89 cases with a cytologic and histologic diagnosis of Hodgkin's disease (HD) and 27 cases with minor or major cytohistologic discrepancies were reviewed. The accuracy of the initial cytologic study was found to be 91.8% for diagnosing HD and 58.1% for classifying its subtypes. Following review, 87 of the 89 agreement cases remained classified as HD. Of the 27 cases with initial cytohistologic discrepancies, 12 were classified as HD and 10 were categorized as lymphocytic or non-Hodgkin's lymphoma by both cytology and histology upon review. Following review, the accuracy of FNA cytology for the diagnosis of HD improved to 98.0%, with 71.4% correct subtyping. The greatest limitation of cytologic subtyping was in cases of nodular sclerotic HD: only 3 of 17 cases could be subtyped even after review. The cytomorphologic features of the HD subtypes are described, and the difficulties encountered in the cytodiagnosis of HD are discussed at length. The results of this study indicate that FNA cytology is a useful tool not only for the diagnosis of HD, but also for its subtyping.     

Computerized morphometric study on fine needle aspirates of cellular follicular lesions of the thyroid

OBJECTIVE: To investigate the value of computerized nuclear morphometry in the differential diagnosis of cellular follicular lesions of the thyroid cytologically diagnosed on fine needle aspiration (FNA) smears. STUDY DESIGN: Sixty cases of FNA thyroid smears were cytologically diagnosed and classified as follows: 30 cases of follicular carcinoma, 20 cases of cellular hyperplastic nodules and 10 cases of follicular adenoma. Using an image analysis system, two morphometric variables, nuclear area and major axis length of the nucleus, were measured for each case. RESULTS: For both nuclear morphometric variables, statistical differences were found between carcinomas and hyperplastic nodules as well as between carcinomas and adenomas. No statistical differences were found between the nuclear variables in either hyperplastic nodules or adenomas. CONCLUSION: The results confirm the aim of our study, to establish nuclear morphometry by computerized image analysis as an additional tool in the differential diagnosis of thyroid follicular lesions cytologically diagnosed on FNA smears.     

Immunocytochemistry in head and neck aspirates. Diagnostic application on direct smears in 16 problematic cases.

This report describes our experience with immunocytochemical staining of routinely processed smears in the fine needle aspiration (FNA) biopsy diagnosis of 16 tumors of the head and neck. Immunocytochemistry (ICC) was performed on alcohol-fixed or air-dried smears using commercially available monoclonal antibodies followed by a streptavidin-biotinylated peroxidase labeling method. In 12 aspirates with cytologically unclassifiable and undifferentiated cells, immunostaining for cytokeratin, leukocyte common antigen, S-100 protein and vimentin provided conclusive evidence of cell lineage. ICC permitted the correct identification and differential diagnosis of four additional tumors: a positive immunoreaction for thyroglobulin identified a metastatic Hürthle cell carcinoma of the thyroid; a coexpression of two distinct classes of intermediate filaments helped support the FNA diagnoses of a parathyroid adenoma and of a synovial sarcoma; and the double immunoreaction for CD15 and CD30 antigens helped identify Reed-Sternberg cells within an unusually suppurative harvest. Two immunostains were required for proper diagnosis in 13 cases and four in the remaining 3. In all cases but one only unstained slides were used. These data demonstrate that immunostaining can conveniently and advantageously be performed on direct smears of aspirated samples of head and neck lesions, but cases should be carefully selected for this procedure.     

Recurrent Hodgkin's disease in the breast. Diagnosis of a case by fine needle aspiration and immunocytochemistry

Recurrent Hodgkin's disease involving the breast in a 17-year-old girl was diagnosed by fine needle aspiration (FNA) biopsy of a solitary mass that developed one year after "curative" radiation. Benign breast disease and breast carcinoma were ruled out upon cytologic examination of the FNA smears, which contained diagnostic Reed-Sternberg cells and the characteristic polymorphic background elements. Follow-up immunoperoxidase staining for Leu-M1 on destained smears confirmed the diagnosis. Definitive therapeutic measures were initiated after the FNA diagnosis.     

Hodgkin's disease presenting as an enlarged thyroid gland. Report of a case diagnosed by fine needle aspiration

An unusual case of Hodgkin's disease (HD) in a 36-year-old woman that was diagnosed by fine needle aspiration (FNA) biopsy of a neck mass believed clinically to be diffuse goiter is reported. The aspirate was composed mainly of dispersed lymphocytes; admixed with these were occasional large mononuclear cells with round-to-oval nuclei and prominent nucleoli. Binucleated variants of the large cells were interpreted as Reed-Sternberg cells, suggesting the diagnosis of HD. Subsequent to the FNA biopsy, radiologic examinations demonstrated an enlarged mediastinum, and incisional biopsy of the neck mass confirmed the diagnosis of HD. This case emphasizes the value of FNA biopsy as a rapid and reliable procedure, even in the unusual but established clinical presentation of HD as a diffuse neck mass.     

Papillary carcinoma of the thyroid gland. Analysis of 94 cases with preoperative fine needle aspiration cytologic examination

From 1979 to 1983, 94 papillary carcinomas of the thyroid gland were examined histologically in our institute after a preoperative cytologic examination. Material for cytologic examination was obtained using fine needle aspiration (FNA) biopsy. Eighty-five (90.4%) of the 94 examined cytologic smears were representative. Among these 85 cases suspicion for malignancy or malignancy itself was found in 64 cases (75.3%). The remaining 21 smears, classified as cytologically not as suspect for malignancy, were reclassified and the previous diagnosis had to be revised in one case. In the other 20 cases no clue for malignancy could be demonstrated even after reexamination. In the 85 cases with representative cytologic findings, tumor size was determined on surgical material, in order to establish how many carcinomas with a diameter less than 3 cm could not be reached by FNA biopsy. Except for one case, all carcinomas with negative preoperative cytologic findings had a diameter less than or equal to 3 cm. The question arising is the possibility of improving the accuracy of FNA biopsy in tumor detection within cold nodules of the thyroid by combined use of scintigraphy and ultrasound-guided FNA biopsy.     

Light and immunoelectronmicroscopic study of Hodgkin’s disease: Evidence of immunoglobulin synthesis by tumor cells

The direct immunoperoxidase technique with peroxidase-conjugated F(ab')2 fragments was used at the light and electron microscopic levels to identify intracytoplasmic immunoglobulin (CIg) components in malignant cells of Hodgkin's disease. In each of the 27 cases studied, Hodgkin and Reed-Sternberg cells contained either IgG or IgM, with both light chains often present simultaneously. The number of IgG-positive malignant cells was inversely related to changes in the lymphoid compartment, as defined by the Rye grading system. The evolution from lymphocytic predominance to lymphocytic depletion was paralleled by a decrease of IgM-positive cells and by a substantial increase (to exclusiveness) of IgG-containing cells. These immunoelectronmicroscopic studies disclosed definite morphologic evidence of CIg synthesis by Hodgkin, Reed-Sternberg and lacunar cells. The immunoglobulin components were also synthesized by lymphoid B cells at different levels of modulation. Immunoglobulin synthesis by malignant cells was localized in perinuclear zone, on free cytoplasmic ribosomes and profiles of rough endoplasmic reticulum. The results of this joint light and electron microscopic study support the view that Hodgkin, Reed-Sternberg and lacunar cells belong to the B-cell compartment within Hodgkin's disease.     

Bone marrow biopsy (BMB). III. Bone marrow biopsy in Hodgkin's disease (HD)

Bone marrow biopsies have been investigated in 330 cases of Hodgkin's disease totalising 298 patients, out of which 32 with repeated biopsies. Positive biopsies with typical lesions were found in 32% of patients, the majority in stages III and IV (88.6%), rarely in stage I or II (11.4%). Nonspecific lesions were very frequent (75%), either isolated or accompanied by typical lesions. The majority of the positive biopsies were found in patients with lymphocytic predominance and lymphocytic depletion, or in polytreated patients in an advanced stage of the disease. The specific marrow involvement consisted in lymphocytic infiltrations either nodular or diffuse, Reed-Sternberg (R-St) or Hodgkin cells. The lymphocytic depletion is often accompanied by diffuse fibrosis, atypical histiocytes, fibroblasts and R-St cells. Hodgkin typical granulomas are rare. The positive biopsies were associated with nonspecific reactions including hyperplasia of granulopoiesis, megakaryocytes, territories with hyperplasia or aplasia, fibrosis, disruption of sinus walls, oedema, plasmocytosis, necrosis, myelomonoblastic cells, lymphocyte nodes, etc. The bone marrow histology has a prognostic significance.     

Grave's disease. Appearance in cytologic smears from fine needle aspirates of the thyroid gland

The cytomorphologic features were analyzed in thyroid samples obtained by fine needle aspiration (FNA) from 54 cases proven to be Grave's disease (toxic goiter) by a multiparameter study. A fire-flare appearance of the follicular cells and a good cellularity of the smears were the features most frequently observed in these cases. Hürthle cell changes were present in 47% of the cases, and small numbers of lymphocytes were seen in smears from 41% of the cases. Epithelioid cell granulomata and multinucleated giant cells were observed in less than one-fourth of the cases. About half of the cases showed some degree of pleomorphism of the follicular cells. Twenty cases of toxic multinodular goiter were similarly analyzed; the features that distinguished this entity from Grave's disease were the absence of epithelioid cells and multinucleated giant cells in the FNA smears.     

Burkitt-type lymphoma. Diagnosis by fine needle aspiration cytology

Forty cases of lymphoma were categorized as Burkitt-type lymphoma in a study of fine needle aspiration (FNA) smears. These constituted 14.3% of all cases of non-Hodgkin's lymphoma diagnosed between 1974 and 1982. The median age was 22 years in these cases, 81.8% of which had extranodal tumors. The majority of the cells in the smears (59.8% +/- 8.32%) were in the 11 micron to 15 micron size range and 60.3% +/- 10.3% had noncleaved nuclei. An average 71% of the cells contained cytoplasmic and/or nuclear vacuolizations. Nonneoplastic macrophages were present in the smears in 87.5% of the cases. A study of paraffin-embedded sections in 17 cases revealed the characteristic "starry-sky" appearance in 11; in 5 it was not clearly appreciated and in 1 the nonneoplastic macrophages were absent. FNA cytology was found to be quite reliable for arriving at a diagnosis of Burkitt-type lymphoma. More than 50% of the cases were managed without resort to subsequent surgical biopsy. Exploratory laparotomy was avoided in 69% of the cases having abdominal tumors.     

Aspiration cytology of Hashimoto's thyroiditis in an endemic area

Fine needle aspiration (FNA) plays a significant role in the diagnosis of thyroid lesions due to its simplicity and low cost. Hashimoto's thyroiditis (HT) is the second most common thyroid lesion next to endemic goitre diagnosed on FNA in iodine (I2) deficient areas. Data on its incidence, prevalence and clinicopathological features in I2 deficient areas is scanty compared to I2 sufficient areas. In the present study the patients presented with HT a decade earlier than reported in I2 sufficient areas. Presentation as a nodular thyroid is common. Diagnosis of HT is likely to be missed in smears showing cytological evidence of hyperplasia or abundant colloid. HT was concurrent in 20 cases of endemic goitre. Careful screening for Hurthle cell change and lymphocytic infiltration into follicular cells should be carried out. In equivocal cases multiple punctures and immunological investigations are helpful. In antibody-negative cases repeat FNA at follow-up is useful. Marked lymphocytic infiltration and Hurthle cell change may indicate a hypothyroid state but hormonal levels are required for clinical management.     

Fine needle aspiration of palpable breast lesions. Results obtained with cytocentrifuge preparation of aspirates

The use of cytocentrifugation in the preparation of fine needle aspiration (FNA) specimens from the breast was evaluated. A total of 174 fine needle aspirates of breast masses were flushed into cytospin Collection Fluid, from which Papanicolaou-stained Cytospin preparations were made in the laboratory. Comparison of these preparations to conventional smears of aspirates showed no significant differences in the number or morphology of the cells. In 148 cases, the FNA cytologic study was followed up by excisional biopsy, Tru-Cut biopsy and/or a combination of mammography and clinical follow-up of two to nine months. Of 36 verified carcinomas, 31 (86%) were correctly diagnosed, with a zero false-positive rate. Among the 74 cytologically benign aspirates, 2 carcinomas were found on open biopsy, giving a false-negative rate of 3%. Lipomas were not diagnosable with this technique. This technique should be considered in institutions with a high turnover of junior staff members, which frequently results in a higher number of poorly smeared specimens or in poorly fixed/air-dried specimens that give suboptimal results with the Papanicolaou stain. With this method, there is less risk of creation of potentially hazardous aerosols and further preparations for additional studies may be made if required.     

Cytodiagnosis of extraosseous mesenchymal chondrosarcoma of meninges: a case report

BACKGROUND: Extraosseous mesenchymal chondrosarcoma (MC) is a rare neoplasm. Most reports in the literature are based on histologic diagnosis. Cases diagnosed on the basis of cytologic features are few. CASE: A 30-year-old woman presented with complaints of headache, vomiting and swelling in the right temporal region for the previous 2 months. Fine needle aspiration (FNA) smears showed scant material consisting mainly of monomorphic small round cells with granular cytoplasm and central round nuclei lying in a background of myxoid matrix. Occasional giant cells were also seen. Cells were periodic acid-Schiff negative. One of the smears showed a tiny fragment of cartilaginous component. A provisional diagnosis of extraosseous MC was made. Peroperatively the mass was arising from meninges and the diagnosis was confirmed by histology. CONCLUSION: Extraosseous MC should be considered in FNA smears showing small round cells in a myxoid background. Demonstration of cartilage and a correlation of clinical presentation and imaging studies with cytologic findings are important.     

Fine needle aspiration of lymphadenopathy in visceral leishmaniasis

OBJECTIVE: To illustrate the cytomorphologic features of Leishmania lymphadenitis associated with visceral leishmaniasis (V/L) and post-kala-azar dermal leishmaniasis (PKDL) and to highlight the fact that Leishmania lymphadenitis must he included in the differential diagnosis of patients presenting with lymphadenopathy, particularly in areas endemic for the disease. STUDY DESIGN: Fine needle aspiration (FNA) was routinely done in 21 cases of lymphadenopathy in VL (18 cases) and PKDL (3 cases), and the detailed cytomorphologic features were correlated with the respective histopathologic findings. RESULTS: Amastigote forms of Leishman-Donovan (LD) bodies were seen in 19 cases both intracellularly, in histiocytes and multinucleate giant cells, and extracellularly. The FNA smears revealed a polymorphous population of cells composed of lymphocytes, histiocytes, plasma cells, giant cells and tingible body macrophages. In a few cases, epithelioid cell granulomas were also seen. The cytomorphologic features were confirmed and correlated on histopathology. CONCLUSION: Not all lymphadenopathy in VL and PKDL is due to Leishmania lymphadenitis. Demonstration of LD bodies on FNA smears helps with the early diagnosis of VL and PKDL with lymphadenopathy where the diseases are endemic.     

Angiosarcoma in FNA smears: diagnostic accuracy,morphology, immunocytochemistry and differential diagnoses

?. Pohar‐Marin?ek and J. Lamovec Angiosarcoma in FNA smears: diagnostic accuracy, morphology, immunocytochemistry and differential diagnoses Objective: The aim of our study was to analyse the diagnostic accuracy in recognizing angiosarcoma from fine needle aspiration (FNA) samples and to determine morphological features of angiosarcoma in cytology. Methods: FNA samples from 18 histologically confirmed angiosarcomas obtained between 1985 and 2009 were included in the study. Original cytological diagnoses were retrieved, smears reviewed and morphological features analysed: cellularity, smear pattern, cell morphology, contents of background. Outcome of immunocytochemistry was noted and additional reactions performed if material was available. Results: There were 13 primary angiosarcomas and five recurrent tumours; nine tumours were epithelioid. Twelve tumours were cytologically diagnosed as malignant, three as suspicious and three were judged unsatisfactory. Only two primary tumours were diagnosed as vascular. According to morphology, tumours were divided into those with predominantly epithelioid cells and those with predominantly spindle cells. Within these two groups were variations due to grade of tumour. Cytomorphology did not correlate well with histology in mixed and spindle cell types of angiosarcomas. Immunocytochemistry was applied in seven cases, specific vascular marker CD31 only twice at the time of diagnosis and three times retrospectively. Conclusions: Angiosarcomas are difficult to recognize on FNA smears when they lack the typical dual, spindle and epithelioid cell population and when they occur in internal organs where carcinomas are more common. Very few reliable data are available concerning specificity of CD31 on cytological material.     

Hodgkin Reed-Sternberg cells express 15-lipoxygenase-1 and are putative producers of eoxins in vivo: novel insight into the inflammatory features of classical Hodgkin lymphoma

Classical Hodgkin lymphoma has unique clinical and pathological features and tumour tissue is characterized by a minority of malignant Hodgkin Reed-Sternberg cells surrounded by inflammatory cells. In the present study, we report that the Hodgkin lymphoma-derived cell line L1236 has high expression of 15-lipoxygenase-1 and that these cells readily convert arachidonic acid to eoxin C(4), eoxin D(4) and eoxin E(4). These mediators were only recently discovered in human eosinophils and mast cells and found to be potent proinflammatory mediators. Western blot and immunocytochemistry analyses of L1236 cells demonstrated that 15-lipoxygenase-1 was present mainly in the cytosol and that the enzyme translocated to the membrane upon calcium challenge. By immunohistochemistry of Hodgkin lymphoma tumour tissue, 15-lipoxygenase-1 was found to be expressed in primary Hodgkin Reed-Sternberg cells in 17 of 20 (85%) investigated biopsies. The enzyme 15-lipoxygenase-1, however, was not expressed in any of 10 biopsies representing nine different subtypes of non-Hodgkin lymphoma. In essence, the expression of 15-lipoxygenase-1 and the putative formation of eoxins by Hodgkin Reed-Sternberg cells in vivo are likely to contribute to the inflammatory features of Hodgkin lymphoma. These findings may have important diagnostic and therapeutic implications in Hodgkin lymphoma. Furthermore, the discovery of the high 15-lipoxygenase-1 activity in L1236 cells demonstrates that this cell line comprises a useful model system to study the chemical and biological roles of 15-lipoxygenase-1.     

Choriocarcinoma metastatic to the breast diagnosed by fine needle aspiration.

Fine needle aspiration (FNA) was used to study nodules in the left breast of a patient with a previous history of uterine choriocarcinoma. The FNA smears contained numerous malignant mononucleated cells and multinucleated giant cells. The cytologic diagnosis was metastatic choriocarcinoma, which was confirmed by histologic study of excised tissue. That diagnosis would have been difficult to make cytologically if the previous history had not been known; the differential diagnosis of multinucleated giant cells in an aspirate from a breast mass is discussed.     

Epithelial atypia in gynecomastia induced by chemotherapeutic drugs. A possible pitfall in fine needle aspiration biopsy.

The clinical, cytopathologic and histopathologic features of a case of gynecomastia induced by chemotherapeutic drugs are described. Fine needle aspiration (FNA) smears showed epithelial atypia, and an erroneous cytologic diagnosis of carcinoma was made. Histopathologic study showed gynecomastia with epitheliosis, papillomatosis and atypical ductal hyperplasia. Review of the FNA smears showed the findings to be more typical of a reparative or regenerative process; these findings had been cytologically overinterpreted, partly due to the lack of adequate clinical information submitted with the aspirate. The possible causes of gynecomastia, the induction of epithelial atypia by cytotoxic chemotherapy and the cytologic features whose recognition may prevent false-positive diagnoses in such cases are discussed.     

Mastopathic fibroadenoma of the breast: a pitfall of aspiration cytology

OBJECTIVE: To assess the correlation between cytological diagnoses and histological subtypes of fibroadenoma (FA) and to clarify the cytological features of a specific group of FA displaying variable features similar to fibrocystic disease (mastopathic type, MFA), and to evaluate the significance of this subtype in cytological diagnosis. METHODS: A review of 141 cases of histologically proven FA was performed. We re-classified them into four subtypes according to Kinoshita's criteria [Jpn J Breast Cancer6 (1991) 377] and further selected 92 cases for which both fine needle aspiration (FNA) smears and histological specimens were available. Among them, 18 cases of MFA and their cytological smears were selected for the present study. RESULTS: There was significant correlation between MFA and cytological diagnosis of 'indeterminate' or 'suspicious for malignancy' (P < 0.01). Although no false-positive diagnosis was experienced in our series, 56% of the MFAs (10/18) had cytological diagnoses of indeterminate or were included in the category 'suspicious for malignancy'. Smears from MFA revealed high cellularity (9/18 smears had more than 10 epithelial clusters each composed of more than 50 cells), presence of cellular discohesiveness (13/18, 72.2%), but only mild nuclear atypia (5/18, 27.8%). Anisonucleosis was present in fewer than half the cases and no apparent condensed chromatin was identified. CONCLUSION: We highlight the significance of subclassification of MFA in aspiration cytology of breast. MFA had a significantly higher chance of falling into the 'suspicious for malignancy' or 'indeterminate' diagnostic category in aspiration cytology. It might be a diagnostic challenge for cytopathologist to identify this subtype of FA in FNA smears.     

Subclassification of localized Leishmania lymphadenitis in fine needle aspiration smears

OBJECTIVE: To describe the cytologic findings of localized Leishmania lymphadenitis and discuss the differential diagnosis. STUDY DESIGN: The study group consisted of 133 cases. All of them were diagnosed by fine needle aspiration (FNA) study. The ages ranged between 3 and 80 years, 102 were male and 31 female. Seventy lymph nodes were excised. RESULTS: The FNA smears revealed a polymorphic population of cells composed of lymphocytes, histiocytes, giant cells, abnormal plasma cells and tingible body macrophages. Leishman-Donovan (LD) bodies were identified in all cases, but their number differed from case to case. Granulomas, dendritic cells, mast cells and lymphoglandular bodies were identified in a substantial number of cases. Depending upon the presence of characteristic cytologic findings, the cases were divided into five major groups: acute inflammation with giant cells, histiocytic granulomas, epithelioid cell granulomas, plasma cell type and mixed histioplasmacytic type. CONCLUSION: Leishmaniasis is an uncommon cause of cervical lymphadenitis but should be considered in the differential diagnosis of unexplained lymphadenopathy in endemic countries. Demonstration of LD bodies is necessary for the diagnosis of this self-limited condition, for which no treatment is required.